Scientists
have pinpointed a cluster of genes that mice need to detect pheromones,
the chemical signals used to modulate sexual and reproductive behavior.
The genes encode protein receptors involved in perceiving pheromones.
Mice born without the receptors have clear deficits: Males have a diminished
sex drive and females are less aggressive in defending their nests.

Karina Del Punta, of The Rockefeller University in New York, and colleagues
used a technique called chromosome engineering to delete 16 pheromone
receptor genes on mouse chromosome 6. The receptors are part of a superfamily
of genes called V1r, which includes about 140 genes. Peter Mombaerts,
also of Rockefeller, led the study.

Researchers have previously characterized V1r genes, but the new
study is the first to demonstrate their role in detecting pheromones.
The mutant mice behave abnormally and are unable to perceive some pheromonal
molecules, according to findings published in Nature.

Much of what is known about pheromones and behavior has come from studies
of mice that no longer have the organ that detects pheromones, the vomeronasal
organ, or VNO. This organ is located in the nasal cavity and can be removed
by surgery.

In the new study, the male mutant mice had a lower sex drive than normal
males. They initiated fewer sexual encounters, but otherwise developed
normally and were fertile. For males that did mount a female, their level
of sexual activity compared similarly to that of normal mice.

Nursing mothers that lacked V1r genes were far less aggressive
in defending their nest area against invaders than normal mothers. In
other respects, however, the females seemed normal. They spent the usual
amount of time retrieving their pups, for instance.

To investigate the cause of this aberrant behavior, the researchers tested
the vomeronasal organ. They detected no electrophysiological response
to three of eight pheromonal molecules in the VNOs of mutant mice. The
loss of receptors was the reason for this, the researchers concluded.

The loss of a subset of V1r genes may 'corrupt' pheromone coding
rather than blocking it, the researchers say, and this may affect mice
in ways that are different than the complete surgical removal of the VNO.
They speculate that the loss of a single Vr gene may be sufficient
to affect behavior.

Earlier this year, researchers reported in Science that deleting
the mouse channel protein TRP2 (for Transient Receptor Protein) caused
males to attempt to mate with other males. Usually, male mice are territorial
and become aggressive around other males.

The study concluded that a major function of the vomeronasal system is
to provide the brain with necessary cues that help males select females
as mates. The researchers reinforced the smell of male mice by splashing
them with urine, which contains pheromones, but the mutant males were
apparently unable to detect the signals.